MARIA CANDIDA BARISSON VILLARES FRAGOSO

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Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina - Médico
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/42 - Laboratório de Hormônios e Genética Molecular, Hospital das Clínicas, Faculdade de Medicina - Líder

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  • article 15 Citação(ões) na Scopus
    Cytoreductive Surgery of the Primary Tumor in Metastatic Adrenocortical Carcinoma: Impact on Patients' Survival
    (2022) SROUGI, Victor; BANCOS, Irina; DAHER, Marilyne; LEE, Jeffrey E.; GRAHAM, Paul H.; KARAM, Jose A.; HENRIQUEZ, Andres; MCKENZIE, Travis J.; SADA, Alaa; BOURDEAU, Isabelle; POIRIER, Jonathan; VAIDYA, Anand; ABBONDANZA, Tiffany; KIERNAN, Colleen M.; RAO, Sarika N.; HAMIDI, Oksana; SACHITHANANDAN, Nirupa; HOFF, Ana O.; CHAMBO, Jose L.; ALMEIDA, Madson Q.; HABRA, Mouhammed Amir; V, Maria C. B. Fragoso
    Context The role of cytoreduction of adrenocortical carcinoma (ACC) remains poorly understood. Objective To analyze the impact of cytoreductive surgery of the primary tumor in patients with metastatic ACC. Design and Setting We performed a multicentric, retrospective paired cohort study comparing the overall survival (OS) in patients with metastatic ACC who were treated either with cytoreductive surgery (CR group) or without cytoreductive surgery (no-CR group) of the primary tumor. Data were retrieved from 9 referral centers in the American-Australian-Asian Adrenal Alliance collaborative research group. Patients Patients aged >= 18 years with metastatic ACC at initial presentation who were treated between January 1, 1995, and May 31, 2019. Intervention Performance (or not) of cytoreductive surgery of the primary tumor. Main outcome and measures A propensity score match was done using age and the number of organs with metastasis (<= 2 or >2). The main outcome was OS, determined from the date of diagnosis until death or until last follow-up for living patients. Results Of 339 patients pooled, 239 were paired and included: 128 in the CR group and 111 in the no-CR group. The mean follow-up was 67 months. Patients in the no-CR group had greater risk of death than did patients in the CR group (hazard ratio [HR] = 3.18; 95% CI, 2.34-4.32). Independent predictors of survival included age (HR = 1.02; 95% CI, 1.00-1.03), hormone excess (HR = 2.56; 95% CI, 1.66-3.92), and local metastasis therapy (HR = 0.41; 95% CI, 0.47-0.65). Conclusion Cytoreductive surgery of the primary tumor in patients with metastatic ACC is associated with prolonged survival.
  • article 0 Citação(ões) na Scopus
    Editorial: Molecular -genetic causes underlying primary adrenal insufficiency: Current insights into diagnosis and treatment
    (2022) V, Maria Candida B. Fragoso; BACHEGA, Tania A. S. S.; DAIN, Liliana
  • article 1 Citação(ões) na Scopus
    Retrospective Analysis of Prognostic Factors in Pediatric Patients with Adrenocortical Tumor from Unique Tertiary Center with Long-Term Follow-Up
    (2022) BACHEGA, Fernanda S.; V, Caio Suartz; ALMEIDA, Madson Q.; BRONDANI, Vania B.; CHARCHAR, Helaine L. S.; LACOMBE, Amanda M. F.; MARTINS-FILHO, Sebastiao N.; SOARES, Ibere C.; ZERBINI, Maria Claudia N.; DENES, Francisco T.; MENDONCA, Berenice; I, Roberto Lopes; LATRONICO, Ana Claudia; V, Maria Candida B. Fragoso
    Pediatric adrenocortical tumors (PACTs) represent rare causes of malignancies. However, the south/southeast regions of Brazil are known to have a high incidence of PACTs because of the founder effect associated with a germline pathogenic variant of tumor suppressor gene TP53. We aimed to retrospectively analyze the types of variables among hormone production, radiological imaging, tumor staging, histological and genetic features that were associated with the occurrence of malignancy in 95 patients (71% females) with PACTs from a unique center. The worst prognosis was associated with those aged > 3 years (p < 0.05), high serum levels of 11-desoxicortisol (p < 0.001), tumor weight >= 200 g (p < 0.001), tumor size >= 5 cm (p < 0.05), Weiss score >= 5 (p < 0.05), Wieneke index >= 3 (p < 0.001) and Ki67 >= 15% (p < 0.05). Furthermore, patients with MacFarlane stage IV had an overall survival rate almost two times shorter than patients with other stages (p < 0.001). Additionally, the subtractions of BUB1B-PINK1 (<6.95) expression (p < 0.05) and IGF-IR overexpression (p = 0.0001) were associated with malignant behavior. These results helped identify patients who are likely to have an aggressive course; further multicenter prospective studies are required to confirm our results. In conclusion, PACTs with these patterns of prognostic factors could be treated using an adjuvant approach that may improve the overall survival in such patients.
  • article 0 Citação(ões) na Scopus
    Pregnancy after pituitary surgery does not influence the recurrence of Cushing's disease
    (2022) LOUSADA, Lia Mesquita; TAPIA, Mariuxi Jacqueline Borja; CESCATO, Valter Angelo Sperling; SILVA, Gilberto Ochman da; MUSOLINO, Nina Rosa Castro; FRAGOSO, Maria Candida Barisson Villares; BRONSTEIN, Marcello Delano; MACHADO, Marcio Carlos
    Purpose Pregnancy is associated with the activation of the hypothalamus-pituitary-adrenal axis, which can cause a misdiagnosis of Cushing's syndrome. The aim of this study is to evaluate the impact of pregnancy after pituitary surgery on the recurrence rate in Cushing's disease (CD) patients. Methods This was a retrospective study in a tertiary center. Between 1990 and 2020, 355 CD patients underwent pituitary surgery. Of those, we included 113 female patients who were <= 45 years old (median age of 32 years, 14-45), PS remission, a follow-up of >= 6 months (median of 122 months, 6-402) and an available obstetric history. Recurrence was defined as the diagnosis of Cushing's syndrome via at least two altered first-line methods. The patients were divided into two subgroups according to pregnancy: no pregnancy or pregnancy prior to CD diagnosis (NP/PP) and pregnancy after CD pituitary surgery (PA). Results Overall, recurrence occurred in 43 out of 113 patients (38%). A higher recurrence rate was seen in the PA subgroup (11/22, 50%), but there was no significant difference between the NP/PP subgroup (32/91, 35%). No difference in survival-free recurrence (SFR) was found between NP/PP and PA subgroups. The lower SFR was related to a higher PS plasma ACTH and normal pituitary at pathological analyses. Conclusions There was no difference in the recurrence rate in patients according to pregnancy history. Other studies with higher numbers of patients are needed to confirm these data.
  • bookPart
    Síndrome de Cushing ACTH-independente
    (2022) FRAGOSO, Maria Candida Barisson Villares; BRONDANI, Vânia Balderrama
  • article 0 Citação(ões) na Scopus
  • bookPart
    Corticotropinomas
    (2022) MACHADO, Márcio Carlos; FRAGOSO, Maria Candida Barisson Villares
  • article 0 Citação(ões) na Scopus
    Rectal leiomyosarcoma as the initial phenotypic manifestation of Li–Fraumeni-like syndrome: a case report and review of the literature
    (2022) SEVERINO, N. P.; WAISBERG, J.; FRAGOSO, M. C. B. V.; LIMA, L. G. C. A. de; BALSAMO, F.; HENRIQUES, A. C.; BIANCO, B.; GEHRKE, F. de Sousa
    Background: Leiomyosarcoma is a rare malignant tumor of smooth muscle origin and represents 10–20% of all soft tissue sarcomas. Primary colon and rectal sarcomas constitute < 0.1% of all large bowel malignancies. In Li–Fraumeni syndrome, sarcomas are the second most frequent cancer (25%). Li–Fraumeni syndrome is a genetic disease with a familial predisposition to multiple malignant neoplasms. This syndrome has an autosomal dominant pattern of inheritance and high penetrance characterized by germline TP53 mutations. Patients with a history of cancer who do not meet all the “classic” criteria for Li–Fraumeni syndrome are considered to have Li–Fraumeni-like syndrome. To the best of our knowledge, this article is the first report of a patient with rectal leiomyosarcoma as the initial phenotypic manifestation of Li–Fraumeni-like syndrome. The authors also present a literature review. Case presentation: A 67-year-old Brazilian woman underwent anterior rectosigmoidectomy and panhysterectomy secondary to rectal leiomyosarcoma. She subsequently developed carcinomatosis and died 2 years after the operation. Her family medical history consisted of a daughter who died at 32 years of age from breast cancer, a granddaughter diagnosed with adrenocortical carcinoma at 6 years of age and two siblings who died from prostate cancer. A genetic study was carried out to identify a pathogenic variant of Li–Fraumeni syndrome. In the DNA extracted from the peripheral blood leukocyte, restriction fragment length polymorphism was analyzed to search for mutations in the TP53 gene. The DNA sequencing identified the germline pathogenic variant p. R337H heterozygous in exon 10 of TP53. The patient was classified as having Li–Fraumeni-like syndrome. Conclusion: In patients with rectal leiomyosarcoma, it is advisable to investigate the family history of cancer and perform genetic studies to screen for Li–Fraumeni syndrome. © 2022, The Author(s).
  • article 19 Citação(ões) na Scopus
    Primary Adrenal Insufficiency Due to Bilateral Adrenal Infarction in COVID-19
    (2022) MACHADO, Iza F. R.; MENEZES, Isabel Q.; FIGUEIREDO, Sabrina R.; COELHO, Fernando M. A.; TERRABUIO, Debora R. B.; V, Davi Ramos; FAGUNDES, Gustavo F. C.; MACIEL, Ana Alice W.; LATRONICO, Ana Claudia; V, Maria Candida B. Fragoso; CANCADO, Eduardo L. R.; MENDONCA, Berenice B.; ALMEIDA, Madson Q.
    Context: Coronavirus disease 2019 (COVID-19) is a proinflammatory and prothrombotic condition, but its impact on adrenal function has not been adequately evaluated. Case report: A 46-year-old woman presented with abdominal pain, hypotension, and skin hyperpigmentation after COVID-19 infection. The patient had hyponatremia, serum cortisol <1.0 mu g/dL, adrenocorticotropin (ACTH) of 807 pg/mL, and aldosterone <3 ng/dL. Computed tomography (CT) findings of adrenal enlargement with no parenchymal and minimal peripheral capsular enhancement after contrast were consistent with bilateral adrenal infarction. The patient had autoimmune hepatitis and positive antiphospholipid antibodies, but no previous thrombotic events. The patient was treated with intravenous hydrocortisone, followed by oral hydrocortisone and fludrocortisone. Discussion: We identified 9 articles, including case reports, of new-onset adrenal insufficiency and/or adrenal hemorrhage/infarction on CT in COVID-19. Adrenal insufficiency was hormonally diagnosed in 5 cases, but ACTH levels were measured in only 3 cases (high in 1 case and normal/low in other 2 cases). Bilateral adrenal nonhemorrhagic or hemorrhagic infarction was identified in 5 reports (2 had adrenal insufficiency, 2 had normal cortisol levels, and 1 case had no data). Interestingly, the only case with well-characterized new-onset acute primary adrenal insufficiency after COVID-19 had a previous diagnosis of antiphospholipid syndrome. In our case, antiphospholipid syndrome diagnosis was established only after the adrenal infarction triggered by COVID-19. Conclusion: Our findings support the association between bilateral adrenal infarction and antiphospholipid syndrome triggered by COVID-19. Therefore, patients with positive antiphospholipid antibodies should be closely monitored for symptoms or signs of acute adrenal insufficiency during COVID-19.
  • article 1 Citação(ões) na Scopus
    N-type calcium channel v2.2 is a target of TCF21 in adrenocortical carcinomas
    (2022) PASSAIA, Barbara Dos Santos; KREMER, Jean Lucas; FRAGOSO, Maria Candida Villares; LOTFI, Claudimara Ferini Pacicco
    Transcription factor 21 (TCF21) directly binds and regulates SF1 mRNA expression in tumor and normal adrenocortical cells, and both are involved in the development and steroidogenesis of the adrenal cortex. TCF21 is a tumor suppressor gene and its expression is reduced in malignant tumors. In adrenocortical tumors, it is less expressed in adrenocortical carcinomas (ACC) than in adrenocortical adenomas (ACA) and normal tissues. However, a comprehensive analysis to identify TCF21 targets has not yet been conducted in any type of cancer. In this study, we performed Chromatin Immunoprecipitation and Sequencing (ChIP-Seq) in an adrenocortical carcinoma cell line (NCI-H295R) overexpressing TCF21, with the aim of identifying TCF21 new targets. The five most frequently identified sequences corresponded to the PRDM7, CNTNAP2, CACNA1B, PTPRN2, and KCNE1B genes. Validation experiments showed that, in NCI-H295R cells, TCF21 negatively regulates the expression of the CACNA1B gene. Recently, it was observed that the N-type calcium channel v2.2 (Cav2.2) encoded by the CACNA1B gene is important in Angiotensin II signal transduction for corticosteroid biosynthesis in NCI-H295R adrenocortical carcinoma cells. Indeed, TCF21 inhibits CACNA1B and Cav2.2 expression in NCI-H295R. In addition, in a cohort of 55 adult patients with adrenocortical tumors, CACNA1B expression was higher in ACC than ACA and was related to poor disease-free survival in ACC patients. These results suggest a mechanism of steroidogenesis control by TCF21 in adrenocortical tumor cells, in addition to the control observed through SF1 inhibition. Importantly, steroid production could impair tumor immunogenicity, contributing to the immune resistance described in adrenal cancer.